Prevalence of 22q11.2 Deletion and Genetic Characterization in Chinese Patients with Congenital Heart Disease

Abstract

BackgroundThe 22q11.2 deletion syndrome, resulted from the rearrangements in the 22q11.2 chromosomal region, is the most common microdeletion syndrome. Most patients share a common 3Mb or 1.5Mb hemizygous deletion of 22q11.2 in the low copy repeats (LCRs). The remaining patients include smaller deletions that are nested within the 3Mb typically deleted region (TDR) and a few rare deletions that have no overlap with the TDR. The present work aimed to identify the prevalence and the detailed genetic characterization of 22q11.2 deletion or amplification in the children with any sporadic congenital heart disease (CHD), and to explore the genotype‐phenotype relationship between deletion/amplification type and clinical data.MethodsA total of 354 CHD patients were screened by multiplex ligation‐dependent probe amplification and capillary electrophoresis methods. Universal Probe Library technology was applied to validate the screening results.ResultsWe found 40 patients in 354 CHD (11.3%) carried different levels of deletions or amplifications. The phenotypes of the 40 patients included ventricular septal defect (15), atrial septal defect (12), patent ductus arteriosus (12), tetralogy of Fallot (6), right ventricular outflow tract stenosis (4), pulmonary stenosis (2), pulmonary hypertension (18), and Down's syndrome (2). Two patients with ventricular septal defect carried the 3Mb TDR from CLTCL1 to HIC2 (LCR A–D) and 1.5Mb deletions from CLTCL1 to MED15 (LCR A–B) respectively; all the others carried atypical deletions or amplifications nested within the LCRs. Based on the gene analysis, CDC45 (15), TBX1 (8), USP18 (8), RTDR1 (7), SNAP29 (6), and ZNF74 (4) exhibited a higher incidence among the 40 individuals; in addition, 6 patients presented a amplification in TOP3B gene.ConclusionsThis study revealed 3Mb TDR, smaller deletions, rare deletions, and segmental amplifications of chromosome 22q11.2 in Chinese CHD patients. The genotype‐phenotype relationship analysis indicated that those gene abnormalities may cause various types of CHD. Our data also suggest that genetic detection should be performed routinely in CHD patients and the unique deletions or amplifications may provide useful insight into individual analysis.Support or Funding InformationSupported by grants from the National Natural Science Foundation of China (81170148 & 81641017), Zhejiang Provincial Natural Science Foundation (LY15H020008), & Tianjin Binhai Key Platform for Creative Research Program (2012‐BK110004), Binhai New Area Health Bureau (2012BWKZ008, 2016BWKY007, 2016BWKZ003).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.